The present invention relates to single-use biomass sensing devices. It also relates to a method for producing such sensors, associated with single-use bioreactors or with a probe/support made of stainless steel on standard bioreactors, made of stainless steel and glass.
The development of novel molecules by biotechnological way is still considered as the main direction of pharmaceutical development. Nowadays, the pharmaceutical industry recognizes significant advantages associated with single use:                safety, due to limitation of the risk of cross-contamination,        and gains in productivity obtained (i) by the reduction of operating costs, in particular labour costs; (ii) by the utilization of a high-density culture which helps to limit culture times and occupation of floor space; and (iii) by a more rapid and less expensive industrial scale application.        
Conventionally the bioreactors utilized are reusable, made of a glass or stainless steel tank, requiring their cleaning, sterilization and constant re-validation. These operations, which are increasingly expensive as a result of continuous growth in regulatory and quality requirements, are eliminated by the introduction of single-use solutions.
There is a growing need for equipment such as single-use fermentation bioreactors, “upstream & downstream” storage and preparation tanks. Such systems are necessarily equipped with sensors provided for measuring physico-chemical, biochemical or biophysical parameters. There can in particular be mentioned sensors carrying out impedance spectroscopy, in particular the capacitive technology sensors designed by the present applicant.
These capacitive sensors make it possible to detect relative variations in capacitances of 10−5 in low-resistance media (a few tens of Ohms). This technique also makes it possible, by means of impedance spectroscopy, to determine the parameters of β dispersion curves (radio frequency). The measurements then provide not only a concentration of living cells but also indications regarding the morphology and the physiological state of the cells. The usual measurement probes are macroscopic in size and intended for stainless steel fermentation tanks. They typically utilize configurations with 4 electrodes in order to be free of the effects of double-layer polarization.
There can in particular be mentioned capacitive sensors specifically dedicated to conductance measurements, in particular for “downstream” type purification applications. These conductance sensors can have the same electrode geometries and structures as capacitive sensors allowing complete measurements of impedance with capacitance and conductance measurements.
The use of an aseptic connector is also known, which makes it possible to introduce solid sensors into a disposable fermenter provided this is in a very protected environment and under a laminar air flow hood. This solution is overall more expensive due to the production and operating cost of the solid sensors: decontamination, removal, cleaning, fitting of the sensor. Moreover, the solid sensors provided in order to equip single-use bioreactors must be sterilized before each use, which does not in itself limit the risk of contamination linked to the sequence of necessary tasks.